Effects of 32P radioactive stents on in-stent restenosis in a double stent injury model of the porcine coronary arteries.

BACKGROUND: The major limitation of coronary stenting remains in-stent restenosis, due to the development of neointimal proliferation. Radioactive stents have demonstrated the ability to reduce this proliferation in the healthy nonatherosclerotic porcine animal model. However, inhibition of tissue proliferation in the in-stent restenotic lesion in a porcine model is not well characterized. The objective of this study was to examine the efficacy and safety of the 32P radioactive stent for the treatment of in-stent restenosis in a double stent injury model of the porcine coronaries. METHODS AND MATERIALS: Eighteen coronary arteries in 9 pigs underwent nonradioactive stent (8 mm in length) implantation. Thirty days after the initial stent implantation, a 32P radioactive stent (18 mm in length) with an activity of 0 and 18 microCi was implanted to cover the initial stent. The swine were killed 30 days after the second stent implantation. Histomorphometric analysis was performed for vessel area (VA), stent strut area (SSA), intimal area (IA), and lumen area (LA). RESULTS: Injury scores, VA, SSA, and LA were similar among the control and radiated groups. Neointimal formation was significantly reduced after placement of radioactive stents as compared to control in both the overlapped (0.93 +/- 0.12 vs. 1.31 +/- 0.51 mm(2), p < 0.05) and nonoverlapped segments (1.14 +/- 0.21 vs. 1.91 +/- 1.04 mm(2), p < 0.05). The smooth muscle cell index in the neointima was reduced. Intimal fibrin was increased in the radiated group as compared to the control (p < 0.01 respectively). CONCLUSIONS: 32P radioactive stents may be safe and effective in reducing neointimal formation leading to in-stent restenosis. Longer follow-up will be required to examine whether these positive findings can be maintained.

Failure of a novel balloon-expandable gamma-emitting ((103)Pd) stent to prevent edge effects.

BACKGROUND: Balloon-expandable beta-particle-emitting ((32)P) stents inhibit within-stent neointimal hyperplasia but induce lumen narrowing beyond the stent margins, ie, the so-called "edge effects." METHODS AND RESULTS: We prospectively investigated the performance of novel stents impregnated with the gamma-emitting isotope (103)Pd, designed to reduce edge effects, in 24 rabbits. The stents had a length of 18 mm and were mounted on 20-mm-long delivery balloons for deployment. Angiograms were obtained immediately and 1 month after direct implantation of control and 1-, 2-, and 4-mCi (103)Pd stents into the iliac arteries without predilatation or postdilatation. Late lumen loss was measured with quantitative angiography. Neointimal hyperplasia and vascular remodeling were evaluated by histomorphometry. Late lumen loss was inhibited within (103)Pd stents (control 0.18 mm, 1 mCi 0.08 mm, 2 mCi 0.05 mm, and 4 mCi -0.03 mm, P<0.05 all activities versus control). Conversely, late lumen loss occurred at the edges of (103)Pd stents, correlating with areas of high balloon/artery ratios and vessel overstretch injury. Edge effects were primarily due to neointimal hyperplasia but were also caused by negative vessel remodeling at high stent activities. CONCLUSIONS: Edge effects after implantation of radioisotope stents can occur independently of the isotope chosen for stent impregnation.

Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia.

OBJECTIVES: We tested the hypothesis that intramyocardial injection of autologous bone marrow (ABM) promotes collateral development in ischemic porcine myocardium. We also defined, in vitro, whether bone marrow (BM) cells secrete vascular endothelial growth factor (VEGF) and macrophage chemoattractant protein-1 (MCP-1). BACKGROUND: The natural processes leading to collateral development are extremely complex, requiring multiple growth factors interacting in concert and in sequence. Because optimal angiogenesis may, therefore, require multiple angiogenic factors, we thought that injection of BM, which contains cells that secrete numerous angiogenic factors, might provide optimal therapeutic angiogenesis. METHODS: Bone marrow was cultured four weeks in vitro. Conditioned medium was assayed for VEGF and MCP-1 and was added to cultured pig aortic endothelial cells (PAEC) to assess proliferation. Four weeks after left circumflex ameroid implantation, freshly aspirated ABM (n = 7) or heparinized saline (n = 7) was injected transendocardially into the ischemic zone (0.2 ml/injection at 12 sites). Echocardiography to assess myocardial thickening and microspheres to assess perfusion were performed at rest and during stress. RESULTS: Vascular endothelial growth factor and MCP-1 concentrations increased in a time-related manner. The conditioned medium enhanced, in a dose-related manner, PAEC proliferation. Collateral flow (ischemic/normal zone X 100) improved in ABM-treated pigs (ABM: 98 +/- 14 vs. 83 +/- 12 at rest, p = 0.001; 89 +/- 18 vs. 78 +/- 12 during adenosine, p = 0.025; controls: 92 +/- 10 vs. 89 +/- 9 at rest, p = 0.49; 78 +/- 11 vs. 77 +/- 5 during adenosine, p = 0.75). Similarly, contractility increased in ABM-treated pigs (ABM: 83 +/- 21 vs. 60 +/- 32 at rest, p = 0.04; 91 +/- 44 vs. 36 +/- 43 during pacing, p = 0.056; controls: 69 +/- 48 vs. 64 +/- 46 at rest, p = 0.74; 65 +/- 56 vs. 37 +/- 56 during pacing, p = 0.23). CONCLUSIONS: Bone marrow cells secrete angiogenic factors that induce endothelial cell proliferation and, when injected transendocardially, augment collateral perfusion and myocardial function in ischemic myocardium.

Long-term effects of intracoronary beta-radiation in balloon- and stent-injured porcine coronary arteries.

BACKGROUND: The data on the long-term safety and efficacy of intracoronary beta-radiation in animal models are limited. METHODS AND RESULTS: A total of 30 coronary arteries in 15 swine were subjected to balloon or stent injury followed by beta-radiation from a centered 32P source (2000 cGy to 1 mm beyond lumen surface) or a sham radiation procedure. The animals received aspirin for 6 months and ticlopidine for 30 days. Five of the 10 animals subjected to radiation died (at 5 days, 7 days, 3 months [n = 2], and 4 months) as a result of layered, occlusive thrombus at the intervention site (3 stent and 2 balloon injury sites). No deaths occurred in the control group. In the surviving animals, balloon-injured and irradiated vessels showed a trend toward larger lumens than controls (2.15 +/- 0.17 versus 1.80 +/- 0.08 mm2, P=0.06) and larger external elastic lamina areas (3.32 +/- 0.21 versus 2.62 +/- 0.10 mm2, P=0.003). In the stent-injured vessels from surviving animals, lumen, neointimal, and external elastic lamina areas were 3.58 +/- 0.33, 3.16 +/- 0.35, and 8.12 +/- 0.42 mm2 for irradiated vessel segments; these values were not different from those in controls (3.21 +/- 0.15, 2.84 +/- 0.27, and 7.76 +/- 0.28 mm2, respectively). Histologically, healing was complete in most survivors, although intramural fibrin and hemorrhage were occasionally seen. CONCLUSION: In the long-term (6 month) porcine model of restenosis, the inhibition by intracoronary beta-radiotherapy of the neointimal formation that is known to be present at 1 month is not sustained. This lack of effect on neointimal formation after balloon and stent arterial injury is accompanied by subacute and late thrombosis that leads to cardiac death on a background of continuous aspirin but relatively brief ticlopidine treatment.

Dose-response study of intracoronary beta-radiation with 32P in balloon- and stent-injured coronary arteries in swine.

PURPOSE: A dose-response study was performed in swine to investigate the vascular effects of 32P over a broad range of doses in order to define the therapeutic window of intracoronary radiotherapy (ICR) with 32P. METHODS AND MATERIALS: A total of 131 porcine arteries were subjected to balloon injury or stenting followed by 0-36 Gy of ICR from a centered 32P source wire to 1 mm beyond lumen surface or a sham ICR procedure. Animals were euthanized at 4 weeks, and vessels were harvested for histomorphometry. RESULTS: In the balloon-injured arteries, doses of 7 and 9 Gy did not impact restenosis. At doses of 14-36 Gy, neointima was markedly reduced, with mild dilatation at the highest dose, 36 Gy. In the stent-injured arteries, the lowest dose of 9 Gy failed to reduce neointimal growth, while 14-26 Gy showed the most favorable response. CONCLUSIONS: ICR with 32P features a broad therapeutic window. Doses of 14-26 Gy to 1 mm beyond lumen surface provided an optimal combination of efficacy and safety. Doses of 7 and 9 Gy were generally ineffective, suggesting a minimum threshold for ICR with 32P to effectively inhibit restenosis.

Effect of percutaneous adenovirus-mediated Gax gene delivery to the arterial wall in double-injured atheromatous stented rabbit iliac arteries.

Though the efficacy of intravascular gene transfer has been demonstrated in native vessels following acute injury, this methodology has not been validated in complex models of vascular injury that more closely mimic clinical angioplasty procedures. Previous studies have shown that Gax gene overexpression modulates the injury-induced remodeling of the vessel in rat carotid and normal rabbit iliac arteries. Here, we evaluated the effect of the Gax gene delivery in atheromatous stented vessels. Rabbits were fed 120 g daily of 1% cholesterol diet for 3 weeks. At 1 week they underwent initial injury on the external iliac artery, then balloon angioplasty was performed at 3 weeks at the same site with a 2.5 mm diameter channel balloon catheter (three times 1 min at 6 atm). Either saline (n = 4) or the control viral construct Ad-CMVluc (5 x 109 p.f.u.) (n = 5) or Ad-CMVGax (5 x 10(9) p.f.u.) (n = 4) was delivered with a poloxamer mixture via a channel balloon (6 atm, 30 min), and a 15 mm long Palmaz-Schatz stent (PS154) was then deployed at the site (1 min, 8 atm). Arteries were analyzed 1 month later. At 1 month, the Ad-CMVGax treated arteries exhibited a lower maximal intimal area (1. 15+/-0.1 mm2) than saline (1.87+/-0.15 mm2, P = 0.007) or Ad-CMVluc-treated vessels (1.98+/-0.31 mm2, P = 0.04). Likewise Ad-CMVGax-treated vessels displayed a lower maximal percentage cross-sectional area narrowing (35.1+/-3.5%) than saline (65.3+/-9.4%, P = 0.01) or Ad-CMVluc-treated vessels (62.7+/-6.7%, P = 0.02). Angiographic analysis revealed larger minimal lumen diameter in Ad-CMVGax treated arteries (2.0+/-0.1 mm) than saline (1.14+/-0.36 mm, P = 0.06) or Ad-CMVluc-treated vessels (1.23+/-0.25 mm, P = 0.02). Overexpression of the Gax gene inhibits neointimal hyperplasia and lumen loss in atheromatous stented rabbit iliac arteries.

Yttrium-90 delivered via a centering catheter and afterloader, given both before and after stent implantation, inhibits neointima formation in porcine coronary arteries.

BACKGROUND: Intracoronary radiation (IR) studies have shown reduction of neointima formation (NF). Extrapolation of animal studies with beta-radiation to clinical trials have shown variable results, which may be related to dosimetry, centering issues, and/or shielding of beta-rays by the stent metal. We examined the effect of yttrium-90 (90Y), a pure beta-emitter delivered via an automatic afterloader to a centering catheter, on the inhibition of NF in balloon-injured (BI) porcine coronary arteries as well as in arteries receiving 90Y either prior to or following stent implantation (SI). METHODS: Twenty-three swine (44 coronary arteries) were studied. In the first study, IR (18 Gy at 1.2 mm from the balloon surface) was administered in 17 arteries following BI, while eight control arteries were subjected to BI only. In the second study, 10 swine (19 coronary arteries) underwent SI. IR (18 Gy) was administered in six arteries before and in eight arteries after SI, while five control arteries received SI only. The animals were sacrificed 2 weeks after BI and 4 weeks after SI. Their coronaries were perfusion fixed and stained, and vessel parameters (intimal area [IA] and medial fracture length [FL]) were analyzed by computer-aided histomorphometry. RESULTS: Arteries subjected to IR following BI had less NF compared to controls (IA/FL = 0.14 +/- 0.2 mm vs. 0.49 +/- 0.2 mm; P = 0.003). IA was reduced significantly in the arteries receiving radiation before and after SI compared to controls (0.92 +/- 0.98 and 0.00 +/- 0/00 vs. 2.72 +/- 1.2 mm2; P = 0.014), despite similar SI in all groups. CONCLUSIONS: IR with 90Y delivered via a centering catheter is safe and effective with complete and homogenous inhibition of NF in the context of BI or SI in the porcine coronary model.

Evaluation of the acute and chronic safety of the biosense injection catheter system in porcine hearts.

Direct myocardial injection of therapeutic agents has been explored as a new method for myocardial revascularization. The integration of a 3D electromechanical mapping catheter with a retractable injection needle should allow for intramyocardial injection to identified sites, obviating the need for open heart surgery. This study assessed the procedural safety and performance characteristics of a novel guided catheter-based transendocardial injection system. The electromagnetic guidance system was coupled with a retrievable 27G needle for left ventricular endocardial injection. Using this system, we injected, transendocardially, methylene-blue (MB) dye tracer at a volume of 0.1 or 0.2 ml per injection in eight normal pigs. Animals were sacrificed acutely, at 1, 3, and 7 days (two animal in each time). Three animals served as controls. The injections were followed by coronary angiography and echocardiogram to assess possible ventricular or coronary perforation and wall motion abnormalities. CK-MB levels were measured up to 24 hr following the procedure. The animals were sacrificed at the assigned time for gross and histopathology evaluation. A total of 101 injections were made in all regions of the heart except the apex and the mitral valve. No animal died as a result of the mapping or injection procedures. Vital signs did not change relative to baseline after the mapping and injection procedures. CK-MB values did not increase over time and there was no evidence of sustained arrhythmia or hemodynamic compromise. There was no evidence of left ventricular or coronary perforation, global or regional wall motion abnormalities, or hemopericardium. On histologic evaluation, the estimated volume of tissue staining was greater than the volume of the injected MB dye due to dispersion of the injectate in the interstitial and intracellular fluid compartments. It is concluded that using this magnetic guidance catheter-based navigational system, it is feasible and safe to perform the transendocardial injection procedure. Thus, if it is determined that direct intramyocardial injection of drugs is a valid therapeutic strategy, this approach offers a clear advantage over surgically based transepicardial injection procedures. Cathet. Cardiovasc. Intervent. 48:447-453, 1999.

Measurement of density and calcium in human atherosclerotic plaque and implications for arterial brachytherapy.

PURPOSE: To measure density of arterial plaque specimens for purposes of improving calculation of intravascular radiation dose. METHODS AND MATERIALS: In the described technique, the mass of the specimen submerged in water is compared with its mass in air. Thirty-three plaque specimens harvested from cadavers and subsequently histologically classified (18 coronary, 15 noncoronary) were subjected to density measurement, and were also assayed for calcium using inductively coupled plasma optical emission spectroscopy (ICPOES). A dose point kernel (DPK) computer model extended to heterogeneous media is used to determine delivered dose to tissues for stents labeled with 32P, 103Pd, and 131Cs, based on measured density values. RESULTS: Plaque specimens identified histologically as noncalcified (non-class VII) had an average density of 1.22 +/- 0.03 g/cm3 (n = 19). Plaque specimens identified as calcified (Class VII) had an average density of 1.45 +/- 0.06 g/cm3 (n = 13). Density of calcified portions of plaque may be even higher because plaque specimens are heterogeneous. Plaque density was found to be correlated with calcium weight percentage (R2 = 0.67) and histologic percent area calcification (R2 = 0.58). Significant variations in calculated dose were found according to isotope, plaque density, and plaque thickness. The assumption of an "all water density" dose model overestimates dose to tissues. For 1-mm thick calcified (class VII) plaque, computed dose to tissues (via DPK model) are decreased by 29%, 34%, and 15%, for 32P, 103Pd, and 131Cs stents, respectively, compared with an "all water density" assumption model, when density is taken into account. Similar decreases are expected for catheter-based brachytherapy systems using beta or low energy (< 100 keV) gamma sources. CONCLUSIONS: This work has importance for radioactive stents and catheter-based brachytherapy due to dependence of dose on density at distances between 0.1 mm and 3 mm away from the radiation source. This dependence is important for both beta- and gamma-based systems.

Validation of the in vivo intravascular ultrasound measurement of in-stent neointimal hyperplasia volumes.

OBJECTIVES: This study was undertaken to validate the in vivo intravascular ultrasound (IVUS) measurement of in-stent neointimal hyperplasia (IH) volumes. BACKGROUND: Because stents reduce restenosis compared to balloon angioplasty, stent use has increased significantly. As a result, in-stent restenosis is now an important clinical problem. Serial IVUS studies have shown that in-stent restenosis is secondary to intimal hyperplasia. To evaluate strategies to reduce in-stent restenosis, accurate measurement of in-stent neointimal tissue is important. METHODS: Using a porcine coronary artery model of in-stent restenosis, single Palmaz-Schatz stents were implanted into 16 animals with a stent:artery ratio of 1.3:1. Intravascular ultrasound imaging was performed at 1 month, immediately prior to animal sacrifice. In vivo IVUS and ex vivo histomorphometric measurements included stent, lumen and IH areas; IH volumes were calculated with Simpson's rule. RESULTS: Intravascular ultrasound measurements of IH (30.4+/-11.0 mm3) volumes correlated strongly with histomorphometric measurements (26.7+/-8.5 mm3, r=0.965, p < 0.0001). The difference between the IVUS and the histomorphometric measurements of IVUS volume was 4.1+/-2.7 mm3 or 15.8+/-11% (standard error of the estimate=0.7). Both histomorphometry and IVUS showed that IH was concentric and uniformly distributed over the length of the stent. Intravascular ultrasound detected neointimal thickening of < or =0.2 mm in 5 of 16 stents. Sample size calculations based on the IVUS measurement of IH volumes showed that 12 stented lesions/arm would be required to show a 50% reduction in IVUS-measured IH volume and 44 stented lesions/arm would be required to show a 25% reduction in IH volume. CONCLUSION: In vivo IVUS measurement of IH volumes correlated strongly with ex vivo histomorphometry. Using volumetric IVUS end points, small sample sizes should be necessary to demonstrate effectiveness of strategies to reduce in-stent restenosis.

Accelerated endothelialization by local delivery of recombinant human vascular endothelial growth factor reduces in-stent intimal formation.

Endothelium plays an important role in vascular smooth muscle cell proliferation and thrombus deposition. We thus hypothesized that local delivery of recombinant human vascular endothelial growth factor (rhVEGF) might reduce in-stent intimal formation. Balloon injury followed by Palmaz-Schatz stent implantation was performed in the external iliac artery of 30 New Zealand rabbits. Animals were then randomized to: 1) no local delivery (Control group, n=10); 2) local delivery via a channel balloon catheter of 100 microg rhVEGF165 (VEGF group, n=10); or 3) local delivery of the vehicle solution (Vehicle group, n=10). Animals were sacrificed 28 days later and morphometric analysis was performed. Maximal intimal area was reduced from 1.47+/-0.12 mm2 and 1.44+/-0.10 mm2 in the Control and Vehicle groups, respectively, to 0.87+/-0.06 mm2 in the VEGF group (p<.001). Accelerated endothelialization by local delivery of an endothelial-specific growth factor, rhVEGF, significantly reduces in-stent intimal formation and could constitute an attractive alternative to direct antiproliferative strategies.

Passivation of metallic stents after arterial gene transfer of phVEGF165 inhibits thrombus formation and intimal thickening.

OBJECTIVES: This study sought to test the hypothesis that direct gene transfer of an endothelial cell mitogen could passivate metallic stents by accelerating endothelialization of the prosthesis. BACKGROUND: Thrombosis and restenosis comprise the principal clinical manifestations of compromised biocompatibility of endovascular stents. Previous studies have demonstrated that endothelial recovery at sites of balloon injury is a critical determinant of consequent intimal thickening and mural thrombus. We therefore investigated the potential for an endothelial cell mitogen delivered as plasmid DNA to optimize stent biocompatibility. METHODS: Naked plasmid DNA encoding vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) (phVEGF165) was delivered locally using a hydrogel-coated balloon angioplasty catheter to 16 rabbit iliac arteries in which metallic stents had been placed at the site of balloon injury; the contralateral iliac artery of each rabbit was balloon injured and stented but not transfected. RESULTS: Stent endothelialization was accelerated by phVEGF165 gene transfer (87.38 +/- 5.06% vs. 33.13 +/- 9.73% [mean +/- SEM] of the planimetered stent surface in the treated vs. contralateral limb, p = 0.005). This was associated with a significant reduction in mural thrombus (3.7 +/- 2.4% vs. 32.7 +/- 9.7%, p = 0.01) at day 7 and intimal thickening (maximal intimal area 0.61 +/- 0.09 vs. 1.44 +/- 0.12 mm2, p < 0.0001) at day 28. No benefit was observed from pCMV-luciferase in 14 similarly instrumented control rabbits. CONCLUSIONS: These findings indicate that arterial gene transfer of naked plasmid DNA encoding for an endothelial cell mitogen may successfully passivate endovascular stents by accelerating stent endothelialization, thereby reducing in-stent thrombus and obstruction due to intimal thickening.

Stent endothelialization. Time course, impact of local catheter delivery, feasibility of recombinant protein administration, and response to cytokine expedition.

BACKGROUND: Because prior studies have established the critical role of the endothelium in preventing vascular thrombosis and intimal thickening, we designed a series of experiments to determine the feasibility of percutaneous local catheter delivery of recombinant protein to accelerate development of an intact endothelial monolayer after stent implantation. METHODS AND RESULTS: Balloon injury followed by percutaneous delivery of a 15-mm-long, balloon-expandable metallic stent was performed in 64 rabbit external iliac arteries (baseline diameter, 2.67 +/- 0.07 mm). Planimetric time-course analysis disclosed < 20% stent endothelialization at 4 days, < 40% at 7 days, and near-complete endothelialization at 28 days. The reporter protein horseradish peroxidase and the endothelial cell-specific recombinant protein vascular endothelial growth factor (VEGF) were each effectively delivered from a local delivery catheter (channel balloon catheter, ChB) after stent implantation. Although local catheter delivery (of vehicle control) itself mildly retarded the extent of stent endothelialization (10.6 +/- 2.9%) versus no local delivery (25.5 +/- 6.6%, P = .045), local ChB delivery of 100 micrograms VEGF overcame this catheter effect: By day 7, stent endothelialization was nearly complete (91.8 +/- 3.8%) (P < .0001 versus no local delivery). Consequently, stent thrombus was reduced in the VEGF-treated group (mural thrombus, 5.3 +/- 3.7%) versus no local delivery (29.3 +/- 6.8%, P = .006). Occlusive thrombus was seen only in the absence of local VEGF administration. CONCLUSIONS: (1) Local delivery of recombinant protein to the arterial wall is feasible after stent implantation, and (2) local delivery of the endothelial cell mitogen VEGF accelerates stent endothelialization, reducing stent thrombosis. These results thus establish a novel means by which the safety and/or bioactivity of endovascular stents may be further enhanced.

Estudio clínico y epidemiológico de un brote de beriberi húmedo en Cartagena de Indias, Colombia, 1992-1993 / Clinical and epidemiologic study of an outbreak of wet beriberi in Cartagena the Indias, Colombia, 1992-1993

La presente investigación ha tenido como objetivo primordial aclarar la etiología de un cuadro clínico caracterizado por edema de las piernas, disestesias con déficit motor en miembros inferiores que, en dos casos, incluyó una cardiopatía que llevó a insuficiencia cardiaca irreversible. Este brote ocurrió entre julio de 1991 y junio de 1993; afectó selectivamente infantes de marina de la Escuela Naval Almirante Padilla en Cartagena de Indias. La metodología se centró en un estudio de casos y controles en el cual se sometió a cada grupo a un cuidadoso interrogatorio, examen clínico, medición por el laboratorio de metales pesados en sangre y orina de 24 horas y estudio de niveles de tiamina en muestras de suero,; se analizaron cuatro biopsias de nervio sural y en el estudio postmorten de los fallecidos se puso especial atención a las alteraciones de miocardio. En muestras ambientales y biológicas, se analizó mercurio, plomo, arsénico y talio. Los resultados totalizan un grupo de 22 infantes de marina con un cuadro muy uniforme sobre todo por las manifestaciones de una neuropatía periférica nutricional, lo cual sumado a la cardiopatía fatal en dos pacientes, cuyo estudio tanto en microscopia de luz como electrónica demostró cambios en todo compatibles con lo observado en beriberi, permiten que se considere que el problema de fondo reune las características del beriberi humedo. Después de concluir que el problema tenía como fondo un origen nutricional basado, en primer lugar, en una falla de tiamina, se hicieron las recomendaciones y ajustes dietéticos indicados para estos casos con una respuesta inmediata y enteramente satisfactoria

Use of stents covered with polytetrafluoroethylene in experimental abdominal aortic aneurysm.

PURPOSE: To establish the effectiveness of covered stents in the treatment of aortic aneurysms, to investigate the histopathologic healing patterns of the device, and to determine the long-term endurance and integrity of modified polytetrafluoroethylene (PTFE). MATERIALS AND METHODS: Experimental aneurysms were created in dogs by enlarging the aortic lumen with a patch of abdominal fascia. After 5 months, eight animals underwent an endoluminal bypass. The bypass device consisted of a 6-cm-long stent covered with thin PTFE. After surgery, the animals were killed at 3, 6, and 12 months in groups of three, three, and two, respectively. Specimens were processed for luminal surface studies and cross-sectional histologic study. Explanted PTFE material was analyzed for its physical characteristics and performance and was compared with retained control samples. RESULTS: Before the animals were killed, aortography showed patent bypass conduits in all animals, although two of eight had leaks into the aneurysmal sac. Endothelialized neointima largely covered the luminal surface of the PTFE stent. The percentage of prosthetic surface covered by tissue did not change from 3 months to 1 year. Physical testing of the explanted PTFE material showed no structural deterioration and no change in the internodal distance. Thickness and axial tensile strength varied 12% and 17% from controls, respectively. CONCLUSION: Thin-walled PTFE seems to have physicochemical characteristics that make this material adequate for endovascular use. Though limited, this study supports the establishment of preliminary clinical evaluation of metallic stents combined with PTFE for the treatment of abdominal aortic aneurysm.

Standardization of conjunctival impression cytology.

Lack of standardization limits the potential of conjunctival impression cytology as a clinical and research tool. This may be attributed to the variety of filter paper currently used. MF Millipore membrane filters of pore sizes 8.0, 3.0, 0.45, 0.22, and 0.025 micron were tested. Samples obtained from 30 eyes of rabbits were randomized and scored by four masked observers for cellularity and morphologic preservation. Cellularity was significantly greater with pore sizes 8.0, 3.0, and 0.45 micron versus 0.22 and 0.025 micron (p < or = 0.001), with an 83% correlation among four scorers. In contrast, morphology was better preserved in the smaller pore size papers (0.22 and 0.025 micron) when compared with larger pore sizes (p = 0.048). Using the best two filter papers (0.22 and 0.025 micron) and an ophthalmodynamometer, either 40, 60, or 80 g of pressure was applied for 3 s to each pore size paper to see whether cellularity could be increased. Cellularity was greater with pore size 0.22 than 0.025 micron (42.3 +/- 19.8 versus 8.7 +/- 6.4). Regardless of the pore size of the filter paper, cellularity was significantly improved at 60 g when compared with either 80 or 40 g. The results show that to maximize cell acquisition, a paper with medium pore size (0.22 micron) and a pressure of 60 g may be the best choice.

Severe diarrhea due to Cokeromyces recurvatus in a bone marrow transplant recipient.

Cokeromyces recurvatus, a sporangiola-forming dimorphic fungus, is a rare cause of urogenital infection in humans. We report here a case of severe watery diarrhea due to C. recurvatus, which was treated successfully with high-dose oral nystatin therapy. We speculate that our patient was probably predisposed to infections due to opportunistic organisms, such as C. recurvatus, because of post-transplantation immunosuppression. To our knowledge, our patient represents the first documented case of diarrhea due to C. recurvatus in man, and this case highlights the potential pathogenic capability of this opportunistic organism in immunosuppressed patients.